Method and apparatus for applying a topical solution

ABSTRACT

An applicator for dispensing a solution having two or more components includes a hollow body having a head provided at one end of the hollow body for dispersion of the solution and a breaking mechanism attached to the hollow body. The breaking mechanism includes at least one projection extendable into an interior of the hollow body. The applicator further includes a plurality of ampoules placed in the interior of the hollow body. The plurality of ampoules contains the two or more components. Upon activation of the breaking mechanism, the at least one projection applies a force to the plurality of ampoules such that the plurality of ampoules break and release the two or more components to form the solution.

CROSS-REFERENCE TO RELATED PATENT APPLICATION

This application is a continuation application of U.S. application Ser.No. 15/371,363, filed Dec. 7, 2016, which claims the benefit of priorityto U.S. Provisional Application No. 62/264,510, filed Dec. 8, 2015, theentire contents of all of which are incorporated herein by reference.

FIELD

The invention relates generally to an apparatus and method forsupplying, mixing, and applying a solution having two or more componentsfor topical use.

BACKGROUND

Photodynamic therapy (PDT), photodynamic diagnosis (PD), orphotochemotherapy is generally used to treat and/or diagnose severaltypes of ailments in or near the skin or other tissues, such as those ina body cavity. During one form of PDT or PD, a patient is firstadministered a photoactivatable agent or a precursor of aphotoactivatable agent that accumulates in the tissue to be treated ordiagnosed. The area in which the photoactivatable agent is administeredis then exposed to visible light, which causes chemical and/orbiological changes in the agent. These changes allow the agent to thenselectively locate, destroy, or alter the target tissue while, at thesame time, causing only mild and reversible damage to other tissues inthe treatment area. One example of a precursor of a photoactivatableagent is 5-aminolevulinic acid (“ALA”), which is commonly used in PDT ofactinic keratosis.

Typically, ALA is administered as a mixed solution with a liquid diluentand topically applied on a patient's skin just prior to treatment.However, a known complication of ALA is its tendency to degrade whenexposed to moisture and/or air. Moreover, degradation of ALA may occurin all sorts of topical vehicles, such as creams, ointments, and solidvehicles. Thus, in order to effectively store ALA until ready fortopical application, it is preferable that the agent is stored in asealed, anhydrous environment.

SUMMARY OF THE INVENTION

One method of storing and administering ALA is through the use of adisposable applicator, such as one disclosed in U.S. Pat. No. 5,954,703,which is incorporated by reference herein in its entirety for thetechniques, methods, compositions, and devices related to theapplication of ALA or other agents for PDT and PD. The applicatorincludes a hermetically-sealed, essentially frangible compartmentenclosed in a deformable container. The frangible compartment may be inthe form of a glass ampoule or vial, which holds ALA. Also contained inthe deformable container is a liquid diluent to be mixed with the ALA.The liquid diluent may also be contained in a second glass ampoule orvial. When ready to apply the ALA solution, a user squeezes thedeformable container such that the ampoule(s) is crushed, allowing theALA and liquid diluent components to mix. The ALA solution is thencontrollably applied directly onto a topical surface by a pointapplicator portion of the container.

In some cases, a large portion of a patient's body is the intendedtreatment area for PDT and/or PD. In these instances, a large portion ofALA solution must be applied to the patient's body prior to treatment.However, in order to supply a sufficient amount of ALA solution using anapplicator such as the one disclosed in U.S. Pat. No. 5,954,703, theapplicator must be “sized up,” including the glass ampoules, in order tostore the proper amount of solution. Such sizing up of the glassampoules, however, may be relatively difficult to achieve because thewalls of the ampoules must remain sufficiently thin to allow for easybreakage. Thus, by increasing the size of the glass ampoules whileretaining the thin walls increases the likelihood of structuralinstability of the ampoules. Moreover, due to pharmaceutical regulatorystandards, it may be preferable to retain the size of the ampoules dueto established data and safe use of certain sized ampoules. In addition,regulations governing pharmaceutical packaging may further constrain theoverall size and basic packaging of the applicator.

In addition, when crushing an applicator such as the one disclosed inU.S. Pat. No. 5,954,703, the user must apply pressure directly to thesurface of the container using his hands. This presents the possibilityof an uneven application of force to the ampoules, resulting in thepossibility that not all of the ampoules are broken. This, in turn, mayreduce the likelihood that the components of the solution are properlymixed before application to the intended treatment area.

Therefore, it is an object of some embodiments of the present inventionto increase the available volume for storage of the ALA solutioncomponents while maintaining a compact structure. It is also an objectof some embodiments of the present invention to provide a sufficientlyreliable and controlled breaking mechanism for the proper mixing of theALA

Solution

In this regard, one embodiment of the present invention includes anapplicator having a plurality of ampoules retained in a compact, hollowbody. In addition, the applicator includes one or more breakingmechanisms formed onto the body of the applicator to ensure consistentand reliable breaking of the ampoules for proper mixing of the solutioncomponents.

BRIEF DESCRIPTION OF THE DRAWINGS

Features, aspects, and advantages of the present invention will becomeapparent from the following description and the accompanying exemplaryembodiments shown in the drawings, which are briefly described below.

FIGS. 1A-1C show top, side, and bottom views of an applicator accordingto an exemplary embodiment.

FIG. 2 shows a detailed view of an applicator head of the applicator ofFIGS. 1A-1C.

FIGS. 3A-3B show schematic bottom and side views of an interior of theapplicator of FIGS. 1A-1C.

FIGS. 4A-4B show perspective views of an applicator according to anotherexemplary embodiment.

FIG. 5 shows a perspective view of the applicator of FIGS. 4A-4B withits case partially removed to illustrate interior components.

FIGS. 6A-6B show perspective views of an applicator according to yetanother exemplary embodiment.

DETAILED DESCRIPTION

FIGS. 1A-1C illustrate one embodiment of an applicator according to thepresent invention. As shown in FIGS. 1A-1C, the applicator 100 is formedas a tertiary structure having a case 10, which includes two separateparts 10 a and 10 b fitted together along a midline, and an applicatorhead 30 attached to one end of the case 10. The case 10 may be generallyoblong in shape, but may be any other appropriate shape, while theapplicator head 30 tapers from the case 10 and narrows to form aball-point tip or other type of applicator tip. The case 10 and theapplicator head 30 may be made of any suitable material. Preferably, thecase 10 and the applicator head 30 are made of a rigid plastic material,such as polyvinyl chloride (PVC).

The applicator head 30 further includes a frame 31 and an applicator pad32 attached to one end of the frame 31. As shown in FIG. 3A, at anopposite end of the frame 31, the frame 31 includes a recessed portion37, which is formed to receive a protrusion 13 formed at an open end ofthe case 10, allowing the applicator head 30 to be snap-fitted onto thecase 10 and resulting in a closed hollow body to hold the solutioncomponents. As shown in FIG. 3A, the frame 31 preferably has a length 35to width 36 ratio of about 1.1 to 1 to allow for increased usability andcomfort. As further shown in FIGS. 3A-3B, the applicator pad 32partially extends into the frame 31, which bows inwardly toward its endsuch that the applicator pad 32 is held in the frame 31 by a form fit.The applicator pad 32 is preferably made from an absorbent material(e.g., cotton, nylon, or a sintered plastic copolymer) such that thedistribution and application of the topical solution contained withinthe applicator 100 may be controlled. The applicator head 30 may alsoinclude a cap 33, shown in greater detail in FIG. 2 . The cap 33 servesto cover the applicator pad 32, which ensures proper sterilization ofthe applicator 100 and its interior components and maintains the sealed,anhydrous environment.

The interior of the applicator 100 includes a plurality of ampoules 22a-22 d encased in a sheath 11. In the exemplary embodiment shown inFIGS. 3A-3B, the plurality of ampoules 22 a-22 d consists of fourampoules. However, the plurality of ampoules is not necessarily limitedto four ampoules and may consist of any number of ampoules, such as two,three, five, or six, or more ampoules. The sheath 11 is preferably madeof a deformable material that is resistant to puncture and/or scoring.For example, the sheath 11 may be made of a plastic material, such aspolyethylene (e.g., low-density polyethylene or high densitypolyethylene), polypropylene, butyrate, propylene copolymers, and otherequivalent materials. Attached to one end of the sheath 11 is a rigidend part 12, which holds the sheath 11 within the case 10. The oppositeend of the sheath 11 is then attached to an attachment flange 34 of theapplicator head 30. This creates a sealed environment closed to moistureand/or air for the ampoules 22 a-22 d. In addition, the sheath 11 servesas a container in which the solution components may be mixed and heldduring application.

Placed within the sheath 11 are the four ampoules 22 a-22 d. Theampoules 22 a-22 d may be formed of a glass material, such asborosilicate, and may be formed to have thin, onion skin-like walls foreasy breakage. In the embodiment shown in FIGS. 3A-3B, two of theampoules 22 a, 22 b are made smaller than the other two ampoules 22 c,22 d. Alternatively, however, the ampoules 22 a-22 d may be of equalsize or each of different sizes. In general, the ampoules 22 a-22 d aresized such that each contain the proper amount of components to ensurethe correct potency and volume of the solution to be applied.

As shown in FIGS. 3A-3B, the smaller of the two ampoules 22 a, 22 b areprovided proximate to the applicator head 30, while the larger of thetwo ampoules 22 c, 22 d are provided distal to the applicator head 30.The ampoules 22 a, 22 b may each be configured with a volume that canhold an amount ranging from about 0.17 mg to about 0.52 mg of anhydrousALA or other component in powder form. In particular embodiments, theampoules 22 a, 22 b are each configured to hold an amount of about 0.345mg of anhydrous ALA or other component in powder form. In addition,ampoules 22 c, 22 d may each be configured to hold a volume, forexample, ranging from about 0.75 ml to about 2.25 ml of a liquiddiluent. In particular embodiments, ampoules 22 c, 22 d are eachconfigured to hold a volume of about 1.5 ml of a liquid diluent. Withthe use of four ampoules, the amount of solution that the applicator 100can hold may be increased. At the same time, the compact shape of theapplicator 100 and the thin walls of the ampoules 22 a-22 d may also beretained in order to maintain ease of breakage and greater constituentvolume. In some embodiments, the applicator 100 may be capable ofdispensing up to a total volume ranging from about 1.5 ml to about 4.5ml of a topical solution. In certain embodiments, the applicator 100 maybe capable of dispensing up to a total volume of about 3 ml of a topicalsolution.

In one embodiment, the ampoules 22 a, 22 b contain essentially anhydrousALA, while the ampoules 22 c, 22 d contain a liquid diluent or, moregenerally, a topical solution vehicle (TSV). Once the ampoules 22 a-22 dhave been filled with the appropriate material, the ampoules 22 a-22 dmay be topped with nitrogen, an inert gas, or evacuated before beinghermetically sealed. Hermetic sealing of the ampoules 22 a-22 d preventsexposing the essentially anhydrous ALA to moisture and/or air and allowsthe solution components to remain separate until ready for application.In addition, due to maintaining a relatively small size with regard tothe individual ampoules, smaller head spaces in each of the ampoules maybe achieved, enhancing stability and allowing less contact withnon-formulation elements (e.g., air and other gases that may be trappedin a given ampoule).

The liquid diluent or TSV may be any suitable diluent or solution thatpermits mixing with the essentially anhydrous ALA. One preferable liquiddiluent that may be used is an alcohol and water solution. The solutionmay also include a wetting agent and/or a humectant. A range ofweight/weight percentages for a preferred solution are 39.9-48.8 Alcohol(USP or SDA 40-2), 39.1-47.8 Purified Water USP, 5.9-7.4 LAURETH-4,3.5-4.3 Isopropyl Alcohol USP, and 1.5-1.8 Polyethylene Glycol 400 NF.The weight/weight percentages of a particularly preferred diluent are44.37 Alcohol (USP or SDA 40-2), 43.46 Purified Water USP, 6.59LAURETH-4, 3.93 Isopropyl Alcohol USP, and 1.65 Polyethylene Glycol 400NF. However, the composition of the liquid diluent or TSV is notparticularly limited. For example, various other alcohol/waterpercentages may be used, various surfactants may be substituted for theLAURETH-4 (e.g., sodium lauryl sulfate, as well as other ionic ornon-ionic surfactants), and propylene glycol or glycerin may besubstituted for the polyethylene glycol.

In order to break the ampoules 22 a-22 d to release its components, theapplicator 100 is provided with a breaking mechanism in the form of twobuttons 40 a, 40 b attached to the case 10, as shown in FIGS. 1A-1B. Asfurther illustrated in FIG. 3B, a connection portion 42 connects thebuttons 40 a, 40 b to one another and further connects the buttons 40 a,40 b to the case 10. The buttons 40 a, 40 b generally include a slopedupper face and an outer flange 43 that serves to guide the movement ofthe buttons 40 a, 40 b within the case 10 as the buttons 40 a, 40 b aredepressed. As shown in FIG. 1A, the sloped upper face of the buttons 40a, 40 b may include grooves and/or depressions 45 that are configured toallow a user's finger to comfortably rest on the buttons 40 a, 40 b whenin use.

As shown in FIG. 3B, formed within an inner portion of the buttons 40 a,40 b is a projection 44. The tip of the projection 44 spans across atleast two of the ampoules (e.g., ampoules 22 a, 22 b) such that when abutton (e.g., button 40 a) is depressed, the projection 44 applies aneven and constant force to the ampoules. This even application of forceallows both ampoules to break simultaneously and reliably when thebutton is pushed by the user. Alternatively, each button (e.g., button40 a) may be provided with two projections 44, each of which crushes oneampoule (e.g., ampoule 22 a). In addition, only one button may beprovided, which may be configured to depress one or more projectionsthat break all four ampoules 22 a-22 d simultaneously. For example, onebutton may be configured to depress connection portion 42, which allowsprojections 44 to simultaneously break and/or crush the ampoules 22 a-22d.

The buttons 40 a, 40 b and the connection portion 42 are preferably madeof a bendable, yet rigid plastic material. Thus, when a user depresses abutton (e.g., button 40 a) in order to break and/or crush the ampoules(e.g., 22 a, 22 b) contained in the sheath 11, the button 40 a rotatesabout a pivot point at its connection to the connection portion 42 asthe outer flange 43 guides the movement of the button 40 a within thecase 10. As the button 40 a rotates, the projection 44 moves downward topress against the sheath 11 and the ampoules 22 a, 22 b. When pressed,the sheath 11 deforms inwardly, but is not punctured by the projection44 and instead remains intact. The ampoules 22 a, 22 b, however, aresimultaneously crushed by the force applied by the projection 44 and itscontents are then released into the sheath 11. Once all ampoules 22 a-22d have been crushed and their contents mixed, the topical solution maythen flow through the applicator pad 32 to be applied to a treatmentarea. In addition, the applicator pad 32 may serve as a filter toprevent the crushed ampoules 22 a-22 d from exiting the applicator 100during application. Moreover, in some embodiments, the buttons 40 a, 40b and the case 10 are sufficiently rigid to prevent unintentionalbreakage of the ampoules 22 a-22 d. For example, the buttons 40 a, 40 bmay be configured so as to require a sufficient force to crush theampoules 22 a-22 d such that unintentional depression of the buttons 40a, 40 b will prevent breakage of the ampoules 22 a-22 d. Alternatively,in other embodiments, the buttons 40 a, 40 b may include a lock or othersafety feature to prevent unintentional depression of the buttons 40 a,40 b. For example, the lock may be a removable tamper-proof safetyfeature that a user may remove from the applicator 100 when needed for afirst time use. In addition, the lock may be a permanent safety featurethat a user may activate or deactivate (e.g., slide into activated ordeactivated positions) to lock or unlock the buttons 40 a, 40 b duringmultiple uses of the applicator 100.

As shown in FIGS. 1A and 1C, the applicator 100 may further include twoindicators 20 a and 20 b. The indicators 20 a, 20 b are formed asapertures located on both the top and bottom parts 10 a, 10 b of thecase 10. In addition, the indicators 20 a, 20 b formed on the top part10 a may be aligned with the indicators 20 a, 20 b formed on the bottompart 10 b such that the user can look directly through the interior ofthe case 10 when held up to a light. The indicators 20 a, 20 b may alsoinclude a transparent material, such as a clear plastic, so as to coverthe sheath 11, or the indicators 20 a, 20 b may simply be holes formedwithin the case 10. The sheath 11 is also made transparent to allow theuser to view the solution contained within the sheath 11.

The indicators 20 a, 20 b may serve to indicate the level of solutionremaining in the applicator 100 during use. In addition, the indicators20 a, 20 b may also allow the user to confirm that the ampoules havebeen properly crushed and/or confirm that the solution has beensufficiently mixed. In the applicator 100 shown in FIGS. 1A and 1B,indicator 20 a is formed as a circular aperture, while indicator 20 b isformed as a larger, oval aperture. In this regard, indicator 20 a mayserve to indicate to the user the level of solution remaining in theapplicator 100 during application of the solution to a patient (i.e.,when the applicator 100 is tilted up in order to allow the solution toflow through the applicator pad 32). On the other hand, indicator 20 bmay serve to indicate proper mixing of the solution when the ampouleshave been crushed and before application of the solution, as theapplicator 100 is being held upright by the user. However, the shape ofthe indicators 20 a, 20 b is not particularly limited, nor is the numberof indicators that may be formed on the case 10.

The components contained in the ampoules 22 a-22 d are also notparticularly limited. Thus, applicator 100 may be configured to storetwo or more incompatible materials that may be later mixed when needed.In addition, the applicator 100 may be configured to hold thermogenicsolutions, which may allow for faster absorption and/or drying whenapplied to the treatment area. Furthermore, the applicator 100 may beconfigured to heat the solution before application of the treatmentarea. This may be preferable when handling solutions that need to beactivated by the application of heat before use or when lending heat tothe solution allows for faster absorption and/or drying. In thisconfiguration, the case 10 further includes a heating wire, in the formof, for example, a copper wire, mounted in the interior of the case 10,but outside of the sheath 11. The copper wire may be inductively heatedin order to heat the formulation after mixing of the components. Whenusing an ALA solution with the applicator 100, copper may affect thestability of the ALA solution and cause the essentially anhydrous ALA todegrade. Thus, by placing the copper wire between the sheath 11 and thecase 10, the ALA solution may be isolated from the copper while stillhaving the benefit of being heated before application for increasedabsorption and/or drying.

According to one method of applying an ALA solution to an intendedtreatment area using the applicator 100, a user first depresses thebutton 40 b of the applicator 100 to simultaneously break the ampoules22 c, 22 d, releasing the liquid diluent into the sheath 11. Next, theuser depresses the button 40 a to simultaneously break the ampoules 22a, 22 b in order to release the essentially anhydrous ALA into thesheath. The user then gently shakes the applicator 100 to mix theessentially anhydrous ALA with the liquid diluent. Alternatively, theuser may depress the button 40 a first or may depress both buttons 40 a,40 b at the same time when mixing the solution.

Once the ampoules have been broken and the contents sufficiently mixed,which may be confirmed by the user using the indicator 20 b as describedabove, the applicator 100 is tilted so that the ALA solution flowstoward the applicator pad 32. Application of the solution isaccomplished by pressing and releasing the applicator pad 32 against thearea to be treated. In some embodiments, only the intended treatmentarea (e.g., a lesion), and not the surrounding skin, is uniformly wettedand then allowed to dry. After the original application has dried, thetreatment may be repeated for multiple applications, preferably for atotal of two applications. Preferably, the topical surface is anexternal surface of a patient, such as the skin. However, internalsurfaces, such as vaginal, rectal, or oral surfaces, may also be treatedaccording to the present invention.

FIGS. 4A-4B and 5 show a second embodiment of an applicator 200. In thisembodiment, the buttons 240 a, 240 b are integrally formed in the case210. The buttons 240 a, 240 b pivotally connect to the case 210 atconnection portions 242. When a user depresses the buttons 240 a, 240 bby pressing down on a pressing knob 245, the buttons 240 a, 240 b pivotdownwardly about the connection portions 242 to press against and deformthe sheath 211 and subsequently crush the ampoules 222 a-222 d (shown inFIG. 5 ) inside the case 210. As shown in FIG. 4B, the applicator 200includes an indicator 220, which can be formed of a transparent materialor simply be a hole formed within the case 210, placed on a side of thecase 210 for viewing of the interior components of the applicator 200.

In addition, as illustrated in FIGS. 4A-4B, the applicator 200 mayfurther include a skin preparation element 250 attached to the case 210at an end opposite to that of the applicator head 230. The skinpreparation element 250 may be used in conjunction with the solution tobe applied for treatment. For example, the skin preparation element 250may take the form of microneedles that can be used to scrape or puncturethe skin prior to application of the solution, such that absorption ofthe solution may be enhanced when applied.

FIGS. 6A-6B show a third embodiment of an applicator 300. The applicator300 is also formed as a tertiary structure and includes a case 310having two parts 310 a and 310 b fitted together at a midline, and anapplicator head 330 attached to one end of the case 310. A breakingmechanism in the form of two buttons 340 a, 340 b connected together bya connecting portion 342 attaches to the case 310. The connectingportion 342 includes lower extending flanges 347, which allow forattachment to the case 310 by a snap-fit. Similar to the applicator 100of the first embodiment, the applicator 300 further includes a sheath311, which holds four ampoules 322 a-322 d, attached to the applicatorhead 330.

As described above, the applicator of the present invention allows for acompact system, which is capable of providing an increased amount ofsolution for the application of larger treatment areas. In addition, theapplicator of the present invention allows for a more reliable method ofstoring and then mixing incompatible materials until just prior toapplication, ensuring greater stability while the components are beingstored and greater consistency when the components are subsequentlymixed. Additional advantages and modifications will readily occur tothose skilled in the art. Therefore, the invention is not limited to thespecific details and representative devices, shown and described herein.Accordingly, various modifications may be made without departing fromthe spirit and scope of the general inventive concept as defined by theappended claims and their equivalents.

What is claimed is:
 1. A method for storing, mixing, and applying asolution having a first component and a second component which inhibitsexposure of the first and second components to air and moisture untiljust prior to application, said method comprising: hermetically sealingthe first component within a first at least one ampoule; hermeticallysealing the second component within a second at least one ampoule;disposing the first at least one ampoule and the second at least oneampoule within a hollow body, the hollow body having: a head fordispersion of the solution; a first breaking mechanism having aprojection extendable into an interior of the hollow body; and a secondbreaking mechanism, the first breaking mechanism and the second breakingmechanism disposed on a side of the hollow body, the first breakingmechanism aligned with the second breaking mechanism; activating thefirst breaking mechanism such that the projection applies a force tobreak the first at least one ampoule and the second breaking mechanismto break the second at least one ampoule and release the first andsecond components from the first at least one ampoule and the second atleast one ampoule; and topically applying the solution having the firstand second components through the head.
 2. The method of claim 1,wherein the first at least one ampoule comprises two ampoules and thesecond at least one ampoule comprises two ampoules.
 3. A method forstoring, mixing, and applying a solution having a first component and asecond component which inhibits exposure of the first and secondcomponents to air and moisture until just prior to application, thefirst component being hermetically sealed within a first at least oneampoule, the second component being hermetically sealed within a secondat least one ampoule, the first at least one ampoule and the second atleast one ampoule disposed within a hollow body having a head fordispersion of the solution, a first breaking mechanism having at leastone projection extendable into an interior of the hollow body to breakthe first at least one ampoule, and a second breaking mechanism to breakthe second at least one ampoule, the first breaking mechanism configuredto rotate about a first pivot point in a plane in a first direction andthe second breaking mechanism configured to rotate about a second pivotpoint in the plane in a second direction opposite the first direction,the first breaking mechanism and the second breaking mechanism disposedon a side of the hollow body, the first breaking mechanism aligned withthe second breaking mechanism, the method comprising: activating thefirst breaking mechanism such that the at least one projection applies aforce to break the first at least one ampoule and the second breakingmechanism to break the second at least one ampoule and mix the first andsecond components from the first at least one ampoule and the second atleast one ampoule; and topically applying the solution having the firstand second components through the head.
 4. The method of claim 3,wherein the topically applying comprises topically applying the solutionto actinic keratosis.
 5. The method of claim 3, wherein activating thefirst breaking mechanism comprises breaking four ampoules.
 6. The methodof claim 3, wherein activating the first breaking mechanism and thesecond breaking mechanism comprises mixing 5-aminolevulinic acid and aliquid diluent for 5-aminolevulinic acid.
 7. The method of claim 3,wherein activating the first breaking mechanism and the second breakingmechanism comprises activating two buttons.
 8. The method of claim 3,further comprising indicating an amount of solution remaining via anindicator.
 9. The method of claim 3, further comprising controllingdispersion of 5-aminolevulinic acid from the head.
 10. The method ofclaim 3, wherein one of the first at least one ampoule and the second atleast one ampoule is configured to store contents having a volume ofabout 0.75 ml to about 2.25 ml, and another of the first at least oneampoule and the second at least one ampoule is configured to storecontents having a weight of about 0.17 mg to about 0.52 mg.
 11. Themethod of claim 3, wherein activating the first breaking mechanismcomprises causing a button to rotate about the first pivot point tocause the at least one projection to press against the first at leastone ampoule.
 12. The method of claim 1, further comprising providing afilter to prevent broken parts of the first at least one ampoule and thesecond at least one ampoule from exiting the head.
 13. The method ofclaim 3, further comprising repeating the topical application of thesolution.
 14. The method of claim 3, wherein the solution is topicallyapplied to an internal surface or an external surface of a patient. 15.The method of claim 7, wherein the two buttons are connected.